Methamphetamine (METH) use is common among human immunodeficiency virus (HIV) infected patients and has the potential to suppress immune response to HIV infection. The general aim of this study is to determine the direct impact of METH on HIV infection and viral- specific immune response. We will use a unique subject population, Chinese METH users, for the proposed study, as most METH users in China are simple users. We hypothesize that METH use impairs specific immune function and promotes HIV replication. In order to address this important hypothesis, we will first examine whether METH use increases HIV infection of macrophages and CD4+ T cells isolated from HIV- METH-using and normal subjects. We will then determine whether in vivo METH exposure affects HIV loads and CD4+/CD8+ T lymphocytes counts. We will also determine the in vivo impact of METH use on the expression of HIV coreceptors (CCR5 and CXCR4) on CD4+ T cells and monocytes and plasma levels of CC-chemokines (MIP-1, 2, and RANTES). These complementary specific aims will provide insights into METH-mediated pathological impact on human immune system and HIV infection. The proposed studies, if successful, will contribute to a better understanding about whether and how METH affects the susceptibility of an individual to HIV infection and promotes viral replication. Our studies also will facilitate a rational basis for practical guidance towards the reduction of the usage of METH among drug abusing population. [unreadable] [unreadable] Project Narrative: This project proposes both ex vivo and in vivo studies using a unique subject population, Chinese METH users, to directly address the role of methamphetamine (METH) in upregulation of HIV infection and impairment of specific immune function. The proposed studies, if successful, will provide direct evidence that METH has a cofactor role in impairing host immune system and promoting HIV replication. [unreadable] [unreadable] [unreadable]